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Prod. Bioprospect."],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Bioactive compounds from food-compatible medicinal herbs have shown promise as preventive agents against age-related neurodegenerative conditions, particularly Alzheimer\u2019s disease (AD). The present work aimed to find Lobetyolin as a new suppressor of A\u03b2 aggregation and its interventions on abnormal metabolism in AD. A\u03b2-expressing <jats:italic>Caenorhabditis elegans<\/jats:italic> (strain CL4176) and wild-type worms were employed to evaluate paralysis onset, lifespan, cerebral A\u03b2 deposition, and intracellular reactive oxygen species (ROS) after Lobetyolin administration. Untargeted ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) metabolomics coupled with RNA-seq transcriptomics was carried out to profile systemic metabolic and gene-expression changes. Differential metabolites and transcripts were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and pathway-impact analyses; hub targets were prioritized by integrating enrichment scores with in-silico docking. Lobetyolin (12.5\u201350\u00a0\u00b5M) markedly protected <jats:italic>C. elegans<\/jats:italic> from A\u03b2-driven toxicity and oxidative stress. In CL2006 worms, \u03b2-amyloid deposits fell by 54.8\u2009\u00b1\u20099.4%, while paralysis in CL4176 was delayed by 20.9\u2009\u00b1\u20094.5%. Lifespan increased by up to 18.2% in CL4176 and 25.0% in wild-type N2 worms. Concomitantly, intracellular ROS declined maximally by 28.1\u2009\u00b1\u20098.9% (N2) and 22.4\u2009\u00b1\u20093.8% (CL4176). Integrative metabolomic\u2013transcriptomic analyses, validated by RT-qPCR, revealed selective remodeling of glutathione metabolism: gst-38 expression was suppressed, whereas gst-1 was elevated. Lobetyolin confers neuroprotective and geroprotective benefits in <jats:italic>vivo<\/jats:italic>, primarily through reprogramming glutathione-centered redox metabolism and selectively modulating glutathione-S-transferases (GST) isoforms. These findings position Lobetyolin as a promising dietary lead compound for AD prevention and healthy aging interventions.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s13659-025-00549-0","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T03:12:23Z","timestamp":1757646743000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lobetyolin, an anti-AD factor from the diet campanulaceae source, metabolism regulation and target exploration"],"prefix":"10.1007","volume":"15","author":[{"given":"Wen","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxue","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7904-2347","authenticated-orcid":false,"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"549_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59055-7","volume":"10","author":"S Zheng","year":"2020","unstructured":"Zheng S. 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